Method and System for Non-Invasive Blood Glucose Detection Utilizing Spectral Data of One or More Components Other Than Glucose

ABSTRACT

A method and system for detecting glucose in a biological sample is disclosed. This includes illuminating a biological sample with a light source, collecting transmitted, transflected or reflected light from the sample with a detector, generating spectral data of one or more components in the sample other than glucose in a spectral data analysis device, and analyzing the spectral data of the one or more components, sufficient to provide a glucose measurement from the spectral data of the one or more components other than glucose with the spectral data analysis device.

CROSS-REFERENCE TO RELATED APPLICATION

This patent application claims priority to U.S. Provisional PatentApplication Ser. No. 61/039,170 filed Mar. 25, 2008, the disclosure ofwhich is incorporated herein by reference.

BACKGROUND OF THE INVENTION

Diabetes is a chronic disease that, when not controlled, over time leadsto serious damage to many of the body's systems, including the nerves,blood vessels, eyes, kidneys and heart. The National Institute ofDiabetes and Digestive and Kidney Diseases (NIDDK) estimates that 23.6million people or 7.8 percent of the population in the United Stateshave diabetes in 2007. Globally, the World Health Organization (WHO)estimates that more than 180 million people have diabetes, a number theyexpect to increase to 366 million by 2030, with 30.3 million in theUnited States. According to the WHO, an estimated 1.1 million peopledied from diabetes in 2005. They project that diabetes deaths willincrease by more than 50% between 2006 and 2015 overall and by more than80% in upper-middle income countries.

The economic burden from diabetes for individuals and society as a wholeis substantial. According to the American Diabetes Association, thetotal annual economic cost of diabetes was estimated to be $174 billionin the United States in 2007. This is an increase of $42 billion since2002. This 32% increase means the dollar amount has risen over $8billion more each year.

A vital element of diabetes management is the self-monitoring of bloodglucose (SMBG) concentration by diabetics in the home environment. Bytesting blood glucose levels often, diabetics can better managemedication, diet and exercise to maintain control and prevent thelong-term negative health outcomes. In fact, the Diabetes Control andComplications Trial (DCCT), which followed 1,441 diabetics for severalyears, showed that those following an intensive-control program withmultiple blood sugar tests each day as compared with thestandard-treatment group had only one-fourth as many people developdiabetic eye disease, one-half as many develop kidney disease, one-thirdas many develop nerve disease, and far fewer people who already hadearly forms of these three complications got worse.

However, current monitoring techniques discourage regular use due to theinconvenient and painful nature of drawing blood through the skin priorto analysis, which causes many diabetics to not be as diligent as theyshould be for good blood glucose control. As a result, non-invasivemeasurement of glucose concentration is a desirable and beneficialdevelopment for the management of diabetes. A non-invasive monitor willmake testing multiple times each day pain-free and more palatable forchildren with diabetes. According to a study published in 2005 (J.Wagner, C. Malchoff, and G. Abbott, Diabetes Technology & Therapeutics,7(4) 2005, 612-619), people with diabetes would perform SMBG morefrequently and have improved quality of life with a non-invasive bloodglucose monitoring device.

Currently, there remains a concentrated effort in academia and industryto develop reliable, affordable non-invasive blood glucose monitors. Onetechnique of non-invasive blood chemicals detection involves collectingand analyzing light spectra data. Extracting information about bloodcharacteristics such as glucose concentration from spectral or otherdata obtained from spectroscopy is a complex problem due to the presenceof components (e.g., skin, fat, muscle, bone, interstitial fluid) otherthan blood in the area that is being sensed. Such other components caninfluence these signals in such a way as to alter the reading. Inparticular, the resulting signal may be much larger in magnitude thanthe portion of the signal that corresponds to blood and therefore limitsthe ability to accurately extract blood characteristics information.

The prevailing view is to correlate the change in optical absorption atcertain wavelengths with blood glucose concentration, while ignoring thefact that similar changes in optical absorption could also be caused byother factors, such as physical exercise, medication, emotion, or achange in body chemistry, such as endocrine levels, etc. As such, goodcorrelations obtained in well controlled laboratory conditions do nottranslate into successful, reliable market devices.

The present invention is directed to overcoming one or more of theproblems set forth above.

SUMMARY OF INVENTION

Embodiments of the present invention relate to a method for detectingglucose in a biological sample. The method includes illuminating abiological sample with a light source, collecting transmitted,transflected or reflected light from the sample, generating spectraldata of one or more components in the sample other than glucose andanalyzing the spectral data of the one or more components sufficient toprovide a glucose concentration measurement from the spectral data ofthe one or more components other than glucose.

These are merely some of the innumerable aspects of the presentinvention and should not be deemed an all-inclusive listing of theinnumerable aspects associated with the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the present invention, reference may bemade to accompanying drawings, in which:

FIG. 1 illustrates a block flow diagram of a method for detectingglucose in a biological sample, according to some embodiments;

FIGS. 2A and 2B illustrate plots of a pulse wave corresponding to lightabsorption of arterial blood in a human finger, according to someembodiments;

FIG. 3 illustrates a graphical view of a water absorbance spectrum,according to some embodiments;

FIG. 4 illustrates a graphical view of an absorbance spectrum of a 1250mg/dL glucose solution, according to some embodiments;

FIG. 5 illustrates a graphical view of an absorbance spectrum of a 2500mg/dL glucose solution, according to some embodiments;

FIG. 6 illustrates a graphical view of differential water spectrum,according to some embodiments; and

FIG. 7 illustrates a system for detecting glucose in a biologicalsample, according to some embodiments.

DETAILED DESCRIPTION OF THE INVENTION

In the following detailed description, numerous exemplary specificdetails are set forth in order to provide a thorough understanding ofthe invention. However, it will be understood by those skilled in theart that the present invention may be practiced without these specificdetails, or with various modifications of the details. In otherinstances, well known methods, procedures, and components have not beendescribed in detail so as not to obscure the present invention.

Embodiments of the invention relate to a method for non-invasive bloodglucose detection. Glucose has extremely weak optical absorption in thevisible (Vis) and near infrared (NIR) regions from about 400 nm to about2500 nm. It is very difficult to accurately determine the concentrationof glucose in a biological sample by determining the portion of opticalabsorption generated by glucose in the biological sample, because theportion of optical absorption by other components is typically severalorders of magnitude larger than that directly by glucose in the twowavelength regions. But, glucose can induce changes in the opticalabsorption of other components in the sample, such as hemoglobin orwater. These changes in optical absorption of components other thanglucose can be used to indirectly determine the concentration of glucosein a biological sample.

Referring to FIG. 1, a block flow diagram of a method for detectingglucose in a biological sample is shown, according to some embodimentsand is generally indicated by numeral 100. In the description of theflowcharts, the functional explanation marked with numerals in anglebrackets <nnn>, will refer to the flowchart blocks bearing that numeral.A biological sample maybe illuminated with a light source <102>.Transmitted, transflected or reflected light may then be collected fromthe sample <104>. Spectral data of one or more components in the sampleother than glucose may be generated <106>. The spectral data of the oneor more components may be analyzed, sufficient to provide a glucoseconcentration measurement from the spectral data of the one or morecomponents other than glucose <108>.

Illuminating <102> may refer to exposing the biological sample to alight source in the visible (Vis), near infrared (NIR) or mid-infraredspectral regions. The wavelength range for illumination <102> may occurbetween about 400 nm and about 10,000 nm, for example. The illuminating<102> may occur between about 400 nm and about 2500 nm or about 400 nmand about 1000 nm, for example. The light source may be lasers, lightemitting diodes (LED), incandescent lamps, halogen lamps or acombination thereof, for example. The light source may be a plurality oflasers. Prior to or after illumination of the sample <102>, a referencesample may be illuminated for calibration.

The biological sample may be any portion of the human body that containsglucose or has the potential to contain glucose. The biological samplemay be a human finger, toe, ear lobe, tongue or arm, for example.

After illumination <102>, transmitted, transflected or reflected lightmay then be collected from the sample <104>. The light may be collectedby one or more detectors or light-sensing devices. An array ofphotodiodes may be utilized, for example.

Spectral data of one or more components in the sample other than glucosemay be generated <106>. The detector may generate a correspondingcurrent signal that is proportional to the power of the light receivedby the detector. The current signal generated by the detector can beconverted to another form of signal, such as an analog voltage signal ora digital signal. Such signals may be converted to spectral orabsorbance data using known processors and algorithms.

The spectral data of the one or more components may be analyzed <108>,sufficient to provide a glucose concentration measurement from thespectral data of the one or more components other than glucose.

Spectroscopic data generation <106> and analysis <108> may be carriedout using a pulsatile or a stationary methodology.

A pulsatile data generation and analysis methodology has been describedin presently owned U.S. patent application Ser. No. 12/245,298, filedOct. 3, 2008, which is incoporated herein by reference and U.S. patentapplication Ser. No. 12/209,807, filed Sep. 12, 2008, which isincoporated herein by reference. When light is transmitted through abiological sample, such as a human finger, the light is absorbed andscattered by various components of the finger including muscle, bone,fat and blood. It has been observed, however, that light absorption by ahuman finger exhibits a small cyclic pattern that corresponds to aheartbeat.

FIG. 2A depicts a plot 202 of a pulse wave that corresponds to the lightabsorption of arterial blood in the capillary due to the heartbeat ofthe user. Although the magnitude of the cyclic pattern is small incomparison to the total photocurrent generated by the detector,considerable information can be extracted from the cyclic pattern of theplot 202. For example, assuming that the person's heart rate is sixtybeats per minute, the time between the start of any pulse beat and theend of that pulse beat is one second. During this one-second period, theplot will have a maximum or peak 204 reading and minimum or valley 206reading. The peak 204 reading of the plot corresponds to when there is aminimum amount of blood in the capillaries, and the valley 206 readingcorresponds to when there is a maximum amount of blood in thecapillaries. By using optical information provided by the peak andvalley of the cyclic plot, the major constituents that are in the bodythat are not in the capillaries, such as fat, muscle (i.e., protein) andinterstitial fluid, are excluded. These major constituents that are notin the capillaries are excluded because they are not likely to changeduring the one-second interval. In other words, the light that isimpeded by the blood can be detected based on the peaks and valleys ofthe plot 202. FIG. 2A illustrates the cyclic pattern on a magnifiedscale. FIG. 2B depicts a more accurate reflection of the cyclic patternin terms of signal amplitude.

In a stationary data acquisition and analysis methodology, the lightabsorption is averaged over a period of time to remove the fluctuationin light absorption due to the heart beat. The glucose concentration canbe extracted from the averaged light absorption at different wavelengthsover the same period of data acquisition time.

Referring again to FIG. 1, analyzing <108> may also includemathematically comparing the changes in absorbance of the one or morecomponents to changes in glucose concentration. Analyzing <108> mayinclude eliminating spectral data of the one or more components forchanges in absorbance not related to interactions with glucose.

Because glucose in the biological sample has such a weak optical signalin the Vis and NIR spectral range, the methods of the present inventiondo not attempt to analyze the glucose signal. Glucose does physically orchemically interact with one or more components in the blood and inducechanges in the optical signal of these components as a function ofglucose concentration. By analyzing the changes in the one or morecomponents, the concentration of glucose in the sample may bedetermined.

EXAMPLE

FIG. 3 shows the NIR spectrum of water between 850 nm to 1100 nm. Astrong positive peak is seen between about 920 nm and 1070 nm. Thespectrum was taken with a Perkin-Elmer™ Lambda-14™ Double BeamUV-Vis-NIR (190 nm to 1100 nm) spectrometer. The scanning speed was 30nm/min, the spectrum resolution was 4 nm, and one data point wascollected per nm. The reference was the air and the sample was HPLCgrade water in a quartz cuvette with 1 cm light path. The baselineabsorbance of the spectrum, about 0.05, is due to reflections from twoair/quartz interfaces and two water/quartz interfaces.

FIG. 4 shows the absorbance spectrum of a 1250 mg/dL solution ofalfa-D(+)-glucose in HPLC grade water, and FIG. 5 shows the absorbancespectrum a 2500 mg/dL solution of alfa-D(+)-glucose in HPLC grade water.The two spectra were taken under the same condition as the waterspectrum in FIG. 3, except that the quartz cuvette containing HPLC gradewater was used as the reference. To minimize the effect of temperatureon water absorption, the two glucose solutions and HPLC grade water wereequilibrated in the sample chamber of the spectrometer for four hoursbefore the measurements.

Both FIG. 4 and FIG. 5 show a large negative peak at about 960 nm, about−0.0018 for the 1250 mg/dL glucose solution and about −0.0030 for the2500 mg/dL glucose solution. This negative peak is not caused by theoptical absorption of glucose in this region. Instead, it is a result ofchange in water absorption due to the presence of glucose. This issupported by the simulated differential water spectrum in FIG. 6. Thesimulated differential water spectrum was obtained by manually redshifting 1 nm of all data points in the water spectrum of FIG. 3, thensubtracting the original water spectrum from the red shifted spectrum.FIG. 6 shows a negative peak centered at 960 nm with a very similar peakshape as those of FIG. 4 and FIG. 5.

FIG. 7 shows an exemplary system for conducting an embodiment of thepresent invention that is generally indicated by numeral 700. The systemof FIG. 7 comprises a light source 701, biological sample 703, detector705, and spectral data analysis device 707. A light source 701 maybelasers, light emitting diodes (LED), incandescent lamps, halogen lampsor a combination thereof, for example. The light source may be aplurality of lasers. A biological sample 703 may be a human finger, toe,ear lobe, tongue or arm. A detector 705 may be any of a wide variety oflight detectors with an illustrative, but nonlimiting, example being anarray of photodiodes. Spectral data analysis device 707 may be anydevice capable of analyzing spectral data as described herein. Anillustrative, but nonlimiting, example of a spectral data analysisdevice 707 may include an SR760™ from Stanford Research Systems, whichis a single-channel 100 kHz FFT spectrum analyzers with a dynamic rangeof 90 dB and a real-time bandwidth of 100 kHz.

Thus, there has been shown and described several embodiments of a novelinvention. As is evident from the foregoing description, certain aspectsof the present invention are not limited by the particular details ofthe examples illustrated herein, and it is therefore contemplated thatother modifications and applications, or equivalents thereof, will occurto those skilled in the art. The terms “have,” “having,” “includes” and“including” and similar terms as used in the foregoing specification areused in the sense of “optional” or “may include” and not as “required.”Many changes, modifications, variations and other uses and applicationsof the present construction will, however, become apparent to thoseskilled in the art after considering the specification and theaccompanying drawings. All such changes, modifications, variations andother uses and applications which do not depart from the spirit andscope of the invention are deemed to be covered by the invention whichis limited only by the claims that follow.

1. A method for detecting glucose in a biological sample, comprising:illuminating a biological sample with a light source; collectingtransmitted, transflected or reflected light from the sample with adetector; generating spectral data of one or more components in thesample other than glucose in a spectral data analysis device; andanalyzing the spectral data of the one or more components, sufficient toprovide a glucose measurement from the spectral data of the one or morecomponents other than glucose with the spectral data analysis device. 2.The method of claim 1, further comprising before or after illuminating,calibrating a light source to a reference sample.
 3. The method of claim1, wherein the light source comprises lasers, light emitting diodes,halogen lamps, incandescent lamps or a combination thereof.
 4. Themethod of claim 1, wherein illuminating comprises exposing thebiological sample to a light source in at least one of the nearinfrared, mid-infrared and visible light regions.
 5. The method of claim1, wherein illuminating comprises exposing the biological sample to alight source in the range of about 400 nm to about 2500 nm.
 6. Themethod of claim 1, wherein collecting comprises collecting transmitted,transflected or reflected light with one or more detectors.
 7. Themethod of claim 1, wherein analyzing spectral data comprises performinga pulsation analysis on the spectral data.
 8. The method of claim 1,wherein analyzing spectral data comprises performing a stationaryanalysis on the spectral data.
 9. The method of claim 1, whereinanalyzing comprises mathematically comparing the changes in absorbanceof the one or more components to changes in glucose concentration. 10.The method of claim 1, wherein analyzing comprises eliminating spectraldata of the one or more components for changes in absorbance not relatedto interactions with glucose.
 11. The method of claim 1, wherein thebiological sample comprises a portion of at least one of a human finger,toe, ear lobe, tongue and arm.
 12. A system for detecting glucose in abiological sample, comprising: a biological sample comprising aplurality of components, the components comprising glucose and at leastone component other than glucose; a light source configured toilluminate the biological sample; a detector configured to collecttransmitted, transflected or reflected light from the sample; and aspectral data analysis device configured to (1) generate spectral dataof one or more components in the sample other than glucose, and (2)analyze the spectral data, sufficient to provide a glucose measurementfrom the spectral data of the one or more components other than glucose.13. The system of claim 12, wherein the light source comprises lasers,light emitting diodes, halogen lamps, incandescent lamps or acombination thereof.
 14. The system of claim 12, wherein the lightsource is configured to emit light in at least one of the near infrared,mid-infrared and visible light regions.
 15. The system of claim 12,wherein the light source is configured to emit light having a wavelengthin the range of about 400 nm to about 2500 nm.
 16. The system of claim12, wherein the detector is configured to collect transmitted,transflected or reflected light.
 17. The system of claim 12, wherein thespectral data analysis device is configured to perform a pulsationanalysis on the spectral data.
 18. The system of claim 12, wherein thespectral data analysis device is configured to perform a stationaryanalysis on the spectral data.
 19. The system of claim 12, wherein thespectral data analysis device is configured to mathematically comparethe changes in absorbance of the one or more components to changes inglucose concentration.
 20. The system of claim 12, wherein the spectraldata analysis device is configured to eliminate portions of the spectraldata that are attributable to changes in absorbance not related tointeractions with glucose.
 21. The system of claim 12, wherein thebiological sample comprises a portion of at least one of a human finger,toe, ear lobe, tongue and arm.